Combination therapy of negative pressure wound therapy and antibiotic-loaded bone cement for accelerating diabetic foot ulcer healing: A prospective randomised controlled trial.

Negative pressure wound therapy (NPWT) and antibiotic-loaded bone cement (ALBC) are commonly used treatments for diabetic foot ulcers (DFUs). However, the combined efficacy of these two modalities remains unclear. This clinical study aimed to assess the effectiveness and underlying mechanisms of NPWT&ALBC in the management of DFUs. A total of 28 patients were recruited, 16 of whom served as controls and received only NPWT, whilst 12 received NPWT&ALBC. Both groups underwent wound repair surgery following the treatments. Blood samples were obtained to detect infections and inflammation. Wound tissue samples were also collected before and after the intervention to observe changes in inflammation, vascular structure and collagen through tissue staining. Compared with the NPWT group, the NPWT&ALBC group exhibited a superior wound bed, which was characterised by reduced inflammation infiltration and enhanced collagen expression. Immunostaining revealed a decrease in IL-6 levels and an increase in α-SMA, CD68, CD206 and collagen I expression. Western blot analysis demonstrated that NPWT&ALBC led to a decrease in inflammation levels and an increase in vascularization and collagen content. NPWT&ALBC therapy tends to form a wound bed with increased vascularization and M2 macrophage polarisation, which may contribute to DFUs wound healing.

Acinetobacter baumannii Bacteriophage: Progress in Isolation, Genome Sequencing, Preclinical Research, and Clinical Application.

Acinetobacter baumannii (A. baumannii) is a common nosocomial pathogen associated with serious clinical challenges owing to its rapidly increasing resistance to antibiotics. Due to their high host specificity and easy access to the natural environment, bacteriophages (phages) may serve as good antibacterial agents. Phage therapy has been successfully used to treat antibiotic-resistant A. baumannii infections. As a fundamental step before phage therapy, the characterization and sequencing of A. baumannii phages have been well studied. Until October 2022, 132 A. baumannii phages have been sequenced and studied, with their genomes ranging from 4 to 234 kb, and we summarize the characterized and sequenced A. baumannii phages. This review is a current and short overview that does not go into detail on the A. baumannii phages. In addition, preclinical studies and clinical applications of A. baumannii phages are also included.

A Modified Suture Technique to Improve Scar Appearance in Wounds Under High Tension.

ABSTRACT: The purpose of this study was to introduce a modified suture technique and to compare its effects on skin scar formation with 2 traditional suture methods: simple interrupted suture (SIS) and vertical mattress suture (VMS). Three groups of healthy adult female Sprague-Dawley rats were selected (6 replicates in each group), and the full-thickness skin of 5 cm × 0.2 cm was cut off on the back of the rats after anesthesia. The wounds were then sutured using 1 of the 3 methods for each group: SIS, VMS, and a newly introduced modified vertical mattress suture (M-VMS) technique with the needle reinsertion at the exit point. A traction device was installed on the back of the rats to achieve high tension wounds. The tensile distance was increased by 1 mm every day for 20 days. After 20 days of healing, the hematoxylin-eosin staining method was used for observation of scar morphology. The collagen production rate was measured by Masson staining, and the type I collagen and type III collagen were detected by the immunofluorescence method. Immunohistochemical staining was used to detect the expression of myofibroblast marker α-smooth muscle actin, and real-time quantitative polymerase chain reaction and Western blot techniques were used to detect the expressions of transforming growth factors TGFß1, TGFß2, and TGFß3 to understand the mechanisms of scar formation. Results showed that the quantity and density of collagen fibers were both lower in the M-VMS group than in the other 2 groups. Immunofluorescence results showed that type I collagen was significantly lower, whereas type III collagen was significantly higher in the M-VMS group than in the other 2 groups. The expressions of α-smooth muscle actin and TGFß1 both were lower in the M-VMS group than in the other 2 groups. The expression of TGFß2 and TGFß3 had no obvious difference among the 3 groups. For wounds under high tension, compared with SIS and VMS methods, the M-VMS technique we proposed can reduce scar formation due to the reduction of collagen formation, myofibroblast expression, and TGFß1 expression.

Pressure does not affect fibrotic function of dermal fibroblast through an in vitro 3D hydrogel culture model.

Pressure therapy has been used for the prevention and treatment of hypertrophic scars for decades. However, the cellular and molecular mechanisms of this treatment modality have not been fully elaborated, leading to long-lasting controversies regarding its clinical effectiveness. In this current study, we adopted an in vitro 3D culture and compression model to explore the effect of pressure force on fibroblasts, in order to further explain the working mechanism of compression force during pressure treatment. Human dermal fibroblasts were cultured in the 3D culture hydrogel and treated with 1.5 atm of external compression force through a syringe tube device, for 4, 8, and 20 h respectively. RNA-seq identified 437 differentially regulated genes after an 8-h compression intervention compared with control cells, among which 256 genes were up-regulated and 181 genes were down-regulated. Further q-PCR analysis confirmed that early growth response 1(EGR1) and c-fos were down-regulated after an 8-h compression intervention. However, the down-regulation of EGR1 and c-fos at the mRNA level does not lead to altered protein synthesis through western blot, for both 8 and 20-h time points after pressure intervention. Genes closely related to the fibrotic function of fibroblasts including type I collagen (COL1), type III collagen (COL3), transforming growth factor ß1(TGF-ß1), matrix metallopeptidase 1 (MMP1), matrix metallopeptidase 1 (TIMP1), connective tissue growth factor (CTGF), α smooth muscle actin (α-SMA), and fibronectin 1 (FN1), were also unaffected after pressure treatment for 8 h. The current study indicated that in our 3D hydrogel culture model, pressure does not directly affect the fibrotic function of dermal fibroblast in vitro. Indirect regulation including reducing oedema, blood perfusion, and tension could be a more possible mechanism of pressure therapy.

Enhancing thermal stability and lytic activity of phage lysin PlyAB1 from Acinetobacter baumannii.

With the increasingly serious drug resistance of Acinetobacter baumannii, there is an increasingly urgent need for new antibacterial drugs. Phage lysin PlyAB1 has a bactericidal effect on drug-resistant A. baumannii, which has the potential to replace antibiotics to fight infection caused by A. baumannii. However, its application is limited by its thermal stability and lytic activity. To solve these problems, molecular dynamics (MD) simulations combined with Hotspot wizard 3.0 were used to identify key residue sites affecting thermal stability, and evolutionary analysis combined with multiple sequence alignment was used to identify key residue sites affecting lytic activity. Four single-point variants with significantly increased thermal stability and four single-point variants with significantly lytic activity were obtained, respectively. Furthermore, by superimposing mutations, we obtained three double-point variants, G100Q/K69R, G100R/K69R, and G100K/K69R, with significantly improved thermal stability and improved lytic activity. At 45°C, the lytic activity and half-life of the optimal variant G100Q/K69R were 1.51- and 24-fold higher than those of the wild PlyAB1, respectively. These results deepen our understanding of the structure and function of phage lysin and contribute to the application of phage lysin in antibiotic substitution.

In situ scarless skin healing of a severe human burn wound induced by a hCTLA4Ig gene-transferred porcine skin graft.

Preventing fibrosis or hypertrophic scar formation following tissue damage is still a big challenge despite the numerous approaches clinicians currently use. Hitherto, no written account was available of a successful case of scarless skin healing after a severe burn injury. Here, we report the first case of the "perfect regenerative healing" of a severe burn wound with no hypertrophic scar formation in which a postage stamp skin autograft was covered with human cytotoxic-T-lymphocyte associated antigen4-immunoglobulin (hCTLA4Ig) gene-transferred pig skin. We also discuss the mechanisms involved in the scarless healing of human burn wounds.

The Interaction of N-Acetylcysteine and Serum Transferrin Promotes Bacterial Biofilm Formation.

BACKGROUND/AIMS: N-acetylcysteine (NAC) is a novel and promising agent with activity against bacterial biofilms. Human serum also inhibits biofilm formation by some bacteria. We tested whether the combination of NAC and human serum offers greater anti-biofilm activity than either agent alone. METHODS: Microtiter plate assays and confocal laser scanning microscopy were used to evaluate bacterial biofilm formation in the presence of NAC and human serum. qPCR was used to examine expression of selected biofilm-associated genes. Extracellular matrix (ECM) was observed by transmission electron microscopy. The antioxidants GSH or ascorbic acid were used to replace NAC, and human transferrin, lactoferrin, or bovine serum albumin were used to replace serum proteins in biofilm formation assays. A rat central venous catheter model was developed to evaluate the effect of NAC on biofilm formation in vivo. RESULTS: NAC and serum together increased biofilm formation by seven different bacterial strains. In Staphylococcus aureus, expression of genes for some global regulators and for genes in the ica-dependent pathway increased markedly. In Pseudomonas aeruginosa, transcription of las, the PQS quorum sensing (QS) systems, and the two-component system GacS/GacA increased significantly. ECM production by S. aureus and P. aeruginosa was also enhanced. The potentiation of biofilm formation is due mainly to interaction between NAC and transferrin. Intravenous administration of NAC increased colonization by S. aureus and P. aeruginosa on implanted catheters. CONCLUSIONS: NAC used intravenously or in the presence of blood increases bacterial biofilm formation rather than inhibits it.

Antimicrobial resistance and virulence genes profiling of methicillin-resistant Staphylococcus aureus isolates in a burn center: A 5-year study.

Methicillin-resistant S. aureus (MRSA) has attracted more and more attention in recent years, especially in burn medical centers. Here we conducted a 5-year period study to evaluate the MRSA infection in our burn center. The staphylococcal chromosomal cassette mec (SCCmec) typing, antimicrobials susceptibility and virulence profiles were also performed among the MRSA isolates. Of the 259 S. aureus isolates, 239 (92.28%) isolates were identified as MRSA. A decreased trend of MRSA isolation rate over time was found (P = 0.0063). Majority of MRSA isolates in our center belonged to SCCmec type III (230/239, 96.23%). Antimicrobials susceptibility tests of the MRSA isolates revealed significantly decreased resistance to clindamycin (P = 0.0183), and increased resistance to chloramphenicol (P = 0.0020) and minocycline (P < 0.0001) over time. Trimethoprim/sulfamethoxazole, clindamycin, vancomycin, teicoplanin and linezolid were suggested to be good choice for MRSA infection in our center. Virulence factors profiling showed that most of MRSA isolates in our center carried the virulence factor pattern of cna-clfA-clfB-eno-fib-icaA-icaD-sea-psmα-lukED-hlg-hlgv-hla-hld (214/239, 89.54%). In conclusion, our study suggests that MRSA infection is serious in our burn center, but presented decreased trend over time. Most of MRSA isolates in our center presented the same virulence factor profile. More attention should be attached to nosocomial infection in burn medical center. Antimicrobials susceptibility changing over time was observed. Antimicrobials susceptibility monitoring is necessary and helps to select appropriate drugs against MRSA infections.

Concurrent CCR7 Overexpression and RelB Knockdown in Immature Dendritic Cells Induces Immune Tolerance and Improves Skin-Graft Survival in a Murine Model.

BACKGROUND/AIMS: Skin transplantation aims to cover skin defects but often fails due to immune rejection of the transplantated tissue. Immature dendritic cells (imDCs) induce immune tolerance but have a low migration rate. After stimulation, imDCs transform into mature DCs, which activate immune rejection. Thus, inducing imDC to obtain a high migration counteracts development of immune tolerance. METHODS & RESULTS: We transfected imDCs with a recombinant adenovirus carrying the CCR7 gene (Ad-CCR7) and a small interfering RNA targeting RelB (RelB-siRNA) to concurrently overexpress CCR7 and downregulate RelB expression. Functionally, such cells showed a significantly enhanced migration rate in the chemotactic assay and decreased T-cell proliferation after lipopolysaccharide stimulation in mixed lymphocyte reactions. Cotransfected cells showed an increased ability to induce immune tolerance by upregulating T regulatory (Treg) cells and shifting the Th1/Th2 ratio. Cotransfection of Ad-CCR7 and RelB-siRNA endowed imDCs with resistance to apoptosis and cell death. CCR7 overexpression and RelB knockdown (KD) in imDCs improve skin-graft survival in a murine skin-transplantation model. CONCLUSION: Transfection with Ad-CCR7 and RelB KD in imDCs may be an effective approach inducing immune tolerance, thus being potentially valuable for inhibiting allograft rejection.

Phage Abp1 Rescues Human Cells and Mice from Infection by Pan-Drug Resistant Acinetobacter Baumannii.

BACKGROUND/AIMS: As an "ESKAPE" pathogen, Acinetobacter baumannii is one of the leading causes of drug-resistant infections in humans. Phage therapy may be a useful strategy in treating infections caused by drug-resistant A. baumannii. Among 21 phage strains that were isolated and described earlier, we investigated the therapeutic efficacy of Abp1 because of its relatively wide host range. METHODS: Phage stability assays were used to evaluate thermal and pH stability of Abp1. Abp1 was co-cultured with A. baumannii (AB1) over a range of multiplicities of infection to determine its bactericidal efficacy. HeLa or THP-1 cells were used in the cytotoxicity and protection assays. Finally, the therapeutic effects of Abp1 on local and systemic A. baumannii infection in mice were determined. RESULTS: We found that Abp1 exhibits high thermal and pH stability and has a low frequency of lysogeny. Bacteriophage resistance also occurs at a very low frequency (3.51±0.46×10-8), and Abp1 can lyse almost all host cells at a MOI as low as 0.1. Abp1 has no detectable cytotoxicity to HeLa or THP-1 cells as determined by LDH release assay. Abp1 can rescue HeLa cells from A. baumannii infection, even if introduced 2 hours post infection. In both local and systemic A. baumannii infection mouse models, Abp1 treatment exhibits good therapeutic effects. CONCLUSION: Abp1 is an excellent candidate for phage therapy against drug-resistant A. baumannii infections.

Astragaloside-IV Alleviates Heat-Induced Inflammation by Inhibiting Endoplasmic Reticulum Stress and Autophagy.

BACKGROUND: Thermal injury is the main cause of pulmonary disease in stroke after burn and can be life threatening. Heat-induced inflammation is an important factor that triggers a series of induces pathological changes. However, this mechanism underlying heat-induced inflammation in thermal inhalation injury remains unclear. Studies have revealed that astragaloside-IV (AS-IV), a natural compound extracted from Astragalus membranaceus, has protective effects in inflammatory diseases. Here, we investigated whether the protective effects of AS-IV occur because of the suppression of heat-induced endoplasmic reticulum (ER) stress and excessive autophagy Methods: AS-IV was administered to Wistar rats after thermal inhalation injury and 16HBE140-cells were treated with AS-IV. TNF-α, IL-6, and IL-8 levels were determined by ELISA and real-time PCR. ER stress and autophagy were determined by western blot. Autophagic flux was measured by recording the fluorescence emission of the fusion protein mRFP-GFP-LC3 by dynamic live-cell imaging. RESULTS: AS-IV had protective effects against heat-induced reactive oxygen species production and attenuated ER stress. AS IV alleviated heat-induced excessive autophagy in vitro and in vivo. Excessive autophagy was attenuated by the PERK inhibitor GSK2656157 and eIF2α siRNA, suggesting that heat stress-induced autophagy can activate the PERK-eIF2α pathway. Beclin 1 and Atg5 siRNAs inhibited the upregulation of the inflammatory cytokines TNF-α, IL-6, and IL-8 after heat exposure. CONCLUSIONS: Thus, AS-IV may attenuate inflammatory responses by disrupting the crosstalk between autophagy and the PERK-eIF2α pathway and may be an ideal agent for treating inflammatory pulmonary diseases.

Unlocking the mystery of the hard-to-sequence phage genome: PaP1 methylome and bacterial immunity.

BACKGROUND: Whole-genome sequencing is an important method to understand the genetic information, gene function, biological characteristics and survival mechanisms of organisms. Sequencing large genomes is very simple at present. However, we encountered a hard-to-sequence genome of Pseudomonas aeruginosa phage PaP1. Shotgun sequencing method failed to complete the sequence of this genome. RESULTS: After persevering for 10 years and going over three generations of sequencing techniques, we successfully completed the sequence of the PaP1 genome with a length of 91,715 bp. Single-molecule real-time sequencing results revealed that this genome contains 51 N-6-methyladenines and 152 N-4-methylcytosines. Three significant modified sequence motifs were predicted, but not all of the sites found in the genome were methylated in these motifs. Further investigations revealed a novel immune mechanism of bacteria, in which host bacteria can recognise and repel modified bases containing inserts in a large scale. This mechanism could be accounted for the failure of the shotgun method in PaP1 genome sequencing. This problem was resolved using the nfi- mutant of Escherichia coli DH5α as a host bacterium to construct a shotgun library. CONCLUSIONS: This work provided insights into the hard-to-sequence phage PaP1 genome and discovered a new mechanism of bacterial immunity. The methylome of phage PaP1 is responsible for the failure of shotgun sequencing and for bacterial immunity mediated by enzyme Endo V activity; this methylome also provides a valuable resource for future studies on PaP1 genome replication and modification, as well as on gene regulation and host interaction.

Antibacterial properties of Acinetobacter baumannii phage Abp1 endolysin (PlyAB1).

BACKGROUND: Acinetobacter baumannii has emerged as one of the most important hospital-acquired pathogens in the world, because of its resistance to almost all available antibiotic drugs. Endolysins from phages are attracting increasing interest as potential antimicrobial agents, especially for drug-resistant bacteria. We previously isolated and characterized Abp1, a virulent phage targeting the multidrug-resistant A. baumannii strain, AB1. METHODS: To evaluate the antimicrobial potential of endolysin from the Abp1 phage, the endolysin gene plyAB1 was cloned and over-expressed in Escherichia coli, and the lytic activity of the recombinant protein (PlyAB1) was tested by turbidity assessment and bacteria counting assays. RESULTS: PlyAB1 exhibits a marked lytic activity against A. baumannii AB1, as shown by a decrease in the number of live bacteria following treatment with the enzyme. Moreover, PlyAB1 displayed a highly specific lytic effect against all of the 48 hospital-derived pandrug-resistant A. baumannii isolates that were tested. These isolates were shown to belong to different ST clones by multilocus sequence typing. CONCLUSIONS: The results presented here show that PlyAB1 has potential as an antibiotic against drug-resistant A. baumannii.

[Clinical diagnosis and treatment of 14 cases of scar cancer ulcer wound on head and face].

Objective: To analyze the clinical characteristics of scar cancer ulcer wound of head and face, and to investigate its diagnosis and treatment. Methods: The clinical data of 14 patients with head and facial scar cancer ulcer wounds who met the selection criteria and admitted between January 2021 and March 2022 were retrospectively analyzed. There were 8 males and 6 females. The age of onset ranged from 21 to 81 years with an average age of 61.6 years. The incubation period ranged from 1 month to 70 years, with a median of 4 years. Site of the disease included 7 cases of head, 6 cases of maxillofacial region, and 1 case of neck region. Injury factors included trauma in 5 cases, scratch in 5 cases, scalding in 2 cases, burn in 1 case, and needle puncture in 1 case. Pathological results showed squamous cell carcinoma in 9 cases, basal cell carcinoma in 3 cases, sebaceous adenocarcinoma in 1 case, papillary sweat duct cystadenoma combined with tubular apocrine sweat gland adenoma in 1 case. There was 1 case of simple extensive tumor resection, 1 case of extensive tumor resection and skin grafting repair, 7 cases of extensive tumor resection and local flap repair, and 5 cases of extensive tumor resection and free flap repair. Results: All the 14 patients were followed up 16-33 months (mean, 27.8 months). Two patients (14.29%) had scar cancer ulcer wound recurrence, of which 1 patient recurred at 2 years after 2 courses of postoperative chemotherapy, and was still alive after oral traditional Chinese medicine treatment. One patient relapsed at 1 year after operation and died after 2 courses of chemotherapy. One patient underwent extensive resection of the left eye and periocular tumor and the transfer and repair of the chimaeric muscle axial flap with the perforating branch of the descending branch of the left lateral circumflex femoral artery, but the incision healing was poor after operation, and healed well after anti-infection and debridement suture. The wounds of other patients with scar cancer ulcer did not recur, and the wounds healed well. Conclusion: Scar cancer ulcer wound of the head and face is common in the middle-aged and elderly male, and the main pathological type is squamous cell carcinoma. Local extensive resection, skin grafting, or flap transfer repair are the main treatment methods. Early active treatment of wounds after various injuries to avoid scar repeated rupture and infection is the foundamental prevention of scar cancer.

A magnetic mucus-penetrating nanoagent boosting phlegm elimination for inhalation injury treatment.

Inhalation injuries arising from exposure to toxic gases or smoke in fires or industrial accidents pose grave risks and significant respiratory complications. The limited efficacy of current treatment strategies stems from challenges in delivering therapeutic agents across the mucus barrier to the damaged trachea and bronchus. This research explores the reparative potential and underlying mechanisms of sputum-penetrable magnetic nanoparticles (MNPs) coated with poly(N-isopropylacrylamide) (PNIPAM), combined with polyethylene glycol (PEG), and loaded with ambroxol hydrochloride (AH) (MNPs@PNIPAM-AH@PEG) as an innovative therapeutic approach for inhalation injuries. The PNIPAM coating, a thermo-responsive polymer, aims to enhance targeted drug release under an external stimulus. The PEG component is designed to mitigate hydrophobic repulsion and electrostatic forces, facilitating nanoagent penetration of the mucus barrier-an obstacle in inhalation injury treatment. PEG's hydrophilicity, combined with the magnetically attracted NPs, enables deep penetration through the mucus layer adhering to the mucus epithelium. Thermal effects break the outer thermal shell of MNPs, accelerating drug release, resolving sputum, and reducing inflammation. The results showed improved therapeutic impact by significantly reducing inflammation, enhancing mucociliary clearance, and promoting tissue repair. Moreover, the MNPs@PNIPAM-AH@PEG NPs showed good biocompatibility and biosafety both in vitro and in vivo. This research underscores the potential of MNPs@PNIPAM-AH@PEG NPs as a novel therapeutic strategy for inhalation injuries, paving the way for innovative treatments in emergency medicine and respiratory care.

A preliminary study of dynamic interactive simulation and computational CT scan of the ideal alveolus model.

BACKGROUND: While the development of CT imaging technique has brought cognition of in vivo organs, the resolution of CT images and their static characteristics have gradually become barriers of microscopic tissue research. PURPOSE: Previous research used the finite element method to study the airflow and gas exchange in the alveolus and acinar to show the fate of inhaled aerosols and studied the diffusive, convective, and sedimentation mechanisms. Our study combines these techniques with CT scan simulation to study the mechanisms of respiratory movement and its imaging appearance. METHODS: We use 3D fluid-structure interaction simulation to study the movement of an ideal alveolus under regular and forced breathing situations and ill alveoli with different tissue elasticities. Additionally, we use the Monte Carlo algorithm within the OpenGATE platform to simulate the computational CT images of the dynamic process with different designated resolutions. The resolutions show the relationship between the kinematic model of the human alveolus and its imaging appearance. RESULTS: The results show that the alveolus and the wall thickness can be seen with an image resolution smaller than 15.6 µm. With ordinary CT resolution, the alveolus is expressed with four voxels. CONCLUSIONS: This is a preliminary study concerning the imaging appearance of the dynamic alveolus model. This technique will be used to study the imaging appearance of the dynamic bronchial tree and the lung lobe models in the future.

Ischemic perfusion radiomics: assessing neurological impairment in acute ischemic stroke.

Introduction: Accurate neurological impairment assessment is crucial for the clinical treatment and prognosis of patients with acute ischemic stroke (AIS). However, the original perfusion parameters lack the deep information for characterizing neurological impairment, leading to difficulty in accurate assessment. Given the advantages of radiomics technology in feature representation, this technology should provide more information for characterizing neurological impairment. Therefore, with its rigorous methodology, this study offers practical implications for clinical diagnosis by exploring the role of ischemic perfusion radiomics features in assessing the degree of neurological impairment. Methods: This study employs a meticulous methodology, starting with generating perfusion parameter maps through Dynamic Susceptibility Contrast-Perfusion Weighted Imaging (DSC-PWI) and determining ischemic regions based on these maps and a set threshold. Radiomics features are then extracted from the ischemic regions, and the t-test and least absolute shrinkage and selection operator (Lasso) algorithms are used to select the relevant features. Finally, the selected radiomics features and machine learning techniques are used to assess the degree of neurological impairment in AIS patients. Results: The results show that the proposed method outperforms the original perfusion parameters, radiomics features of the infarct and hypoxic regions, and their combinations, achieving an accuracy of 0.926, sensitivity of 0.923, specificity of 0.929, PPV of 0.923, NPV of 0.929, and AUC of 0.923, respectively. Conclusion: The proposed method effectively assesses the degree of neurological impairment in AIS patients, providing an objective auxiliary assessment tool for clinical diagnosis.

eIF6 modulates skin wound healing by upregulating keratin 6B.

Eukaryotic translation initiation factor 6 (eIF6) plays a crucial role in 60S ribosome biogenesis and protein translation, as well as in hypertrophic scar formation, but its potential role in epithelialization is still poorly understood. Herein, we found that eIF6 negatively correlated with the wound healing process. Mice with genetically knockdown eIF6 (eIF6+/-) showed faster re-epithelization as shown by the longer tongue of the newly formed epidermis. Furthermore, eIF6 ablation accelerated the wound healing process by targeting basal keratinocytes in the eIF6 keratinocyte-conditional knockout (eIF6f/+; Krt5-Cre+) mice. Mechanistically, keratin 6B, an important wound-activated protein, was significantly upregulated in eIF6f/+; Krt5-Cre+ mice skin as proved by RNA-seq, western immunoblots, and immunofluorescence staining. Moreover, an elevated level of KRT6B and accelerated proliferative capacity were also observed in stable knockdown eIF6 HaCaT cells. Taken together, eIF6 downregulation could accelerate epithelialization by upregulating KRT6B expression and promoting keratinocyte proliferation. Our results for the first time indicate that eIF6 might be a novel target to regulate re-epithelialization.

Characterization and genome sequencing of phage Abp1, a new phiKMV-like virus infecting multidrug-resistant Acinetobacter baumannii.

While screening for alternative antibiotics against multidrug-resistant Acinetobacter baumannii, we isolated a virulent A. baumannii bacteriophage Abp1. Transmission electron microscopy revealed that the phage had an icosahedral head with a short tail and should be classified as a member of the Podoviridae family. SDS-PAGE showed that Abp1 contained at least one major and nine minor proteins. In a single-step growth test, we demonstrated that Abp1 had a latent period of 10 min and a burst size of 350. Abp1 also had a relatively narrow host range. The entire genome was sequenced, and the final assembly yielded a 42,185 bp, linear, double-stranded DNA molecule with a G+C content of 39.15 % and containing 54 putative genes. Among these genes, 26 were functionally known, leaving 28 unknown putative genes. Abp1 is a new member of the phiKMV-like virus subgroup of the T7 group; its genome sequence is very similar to that of the A. baumannii phage phiAB1.

Mussel-Derived Bioadaptive Artificial Tendon Facilitates the Cell Proliferation and Tenogenesis to Promote Tendon Functional Reconstruction.

Tendon injuries range from acute-related trauma to chronic-related injuries are prevalent and bring substantial pain, functional loss, and even disability to the patients. The management of tendon injuries is tricky due to the innate limited regenerative capability of the tendon. Currently, surgical intervention of tendon injuries with artificial tendons remains the standard of care. However, most of artificial tendons are manufactured with synthetic materials, which possess relatively poor biomimetic characteristics and inadequate inherent biodegradability, hence rendering limited cell proliferation and migration for tendon healing. To address these limitations, this work develops a mussel-derived artificial tendon based on double-cross-linked chitosan modification. In this design, decellularized artificial tendon serves as a natural biomimetic scaffold to facilitate the migration and adhesion of tendon repair cells. Additionally, as the cells proliferate, the artificial tendon can be degraded to facilitate tendon regeneration. Moreover, the chitosan cross-linking further enhances the mechanical strength of artificial tendon and offers a controllable degradation. The in vitro and in vivo experimental results demonstrate that mussel-derived artificial tendon not only accelerate the tendon functional reconstruction but also enable harmless clearance at postimplantation. The finding provides a promising alternative to conventional artificial tendons and spurs a new frontier to explore nature-derived artificial tendons.